PROJECT SUMMARY/ABSTRACT Adolescent girls and young women (AGYW) in sub-Saharan Africa are highly vulnerable to HIV. In Kenya, youth ages 15?24 account for 33% of new infections annually, and incidence is twice as high in AGYW as it is in young men. Pre-exposure prophylaxis (PrEP) is a powerful tool to reduce HIV acquisition, but adherence has been low among AGYW, limiting its protective benefit. PrEP stigma?typically based on stereotypes of users as ?promiscuous? or HIV-positive?is emerging as a key barrier to adherence. However, evidence among AGYW is limited. The goal of the proposed study is to improve our understanding of stigma- related barriers to PrEP adherence among AGYW in Kenya and identify potential intervention approaches and targets. The study will build on our recent research to adapt the Health Stigma and Discrimination Framework for PrEP stigma among AGYW and will leverage our successful partnership with Impact Research and Development Organization (IRDO), which is implementing the DREAMS Initiative in Siaya County, Kenya and has initiated more than 3,900 AGYW on PrEP. We will build stigma research capacity at IRDO by mentoring early-career Research Associates and training local AGYW youth researchers. The specific aims are to (1) develop and validate a scaled instrument to measure relevant dimensions of PrEP stigma among AGYW who use PrEP, and (2) assess the relationship between stigma and PrEP adherence and identify intervention targets. Aim 1 will use youth-led participatory research to refine the PrEP stigma framework with AGYW, identify key components of PrEP stigma, and understand how related types of stigma (HIV, gender, and sexuality) overlap with PrEP stigma. Findings will inform the development of the initial scale. After cognitive testing, the scale will be piloted with 200 AGYW to confirm the hypothesized factor structure and assess reliability and construct validity, including whether it is distinct from other types of stigma. Aim 2 will use a mixed methods approach. For Aim 2a, we will conduct a quantitative survey with 300 AGYW PrEP users to determine the prevalence of various types and dimensions of stigma impacting AGYW, measuring PrEP stigma with the Aim 1 scale. Participants will be prospectively followed using DREAMS program data to test the association of baseline stigma with PrEP adherence (both persistence and execution) over the next 6 months. For Aim 2b, we will conduct qualitative focus group discussions with AGYW and their key influencers (family members, peers, partners, and health care providers) to understand stigmatizing attitudes and behaviors and assess the acceptability of candidate interventions. The qualitative and quantitative findings will be integrated to identify future intervention targets and approaches. This study?s focus on PrEP stigma among Kenyan AGYW is innovative and fills a critical gap in efforts to end the HIV epidemic. The findings will lay the groundwork to develop and test a culturally tailored, age-appropriate stigma reduction intervention, which will aim to increase PrEP adherence in this vulnerable population.